7-106001586-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152750.5(CDHR3):c.838A>G(p.Ser280Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDHR3 NM_152750.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.04

Genes affected

CDHR3 (HGNC:26308): (cadherin related family member 3) Predicted to enable cadherin binding activity and calcium ion binding activity. Predicted to be involved in calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules; cell morphogenesis; and cell-cell junction organization. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11883271).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDHR3	NM_152750.5	c.838A>G	p.Ser280Gly	missense_variant	7/19	ENST00000317716.14
CDHR3	NM_001301161.2	c.574A>G	p.Ser192Gly	missense_variant	6/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDHR3	ENST00000317716.14	c.838A>G	p.Ser280Gly	missense_variant	7/19	1	NM_152750.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 29, 2023

The c.838A>G (p.S280G) alteration is located in exon 7 (coding exon 7) of the CDHR3 gene. This alteration results from a A to G substitution at nucleotide position 838, causing the serine (S) at amino acid position 280 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
Cadd	Benign	18
Dann	Uncertain	0.99
DEOGEN2	Benign	0.0036	T;T;.
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.52	T;T;T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L;.;.
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Benign	0.037
Sift	Benign	0.39	T;T;T
Sift4G	Benign	0.085	T;T;T
Polyphen		0.080	B;.;.
Vest4		0.17
MutPred		0.47		Gain of ubiquitination at K281 (P = 0.1245);.;.;
MVP		0.29
MPC		0.035
ClinPred		0.23	T
GERP RS		3.3
Varity_R		0.10
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-105642032; COSMIC: COSV58421559;